A General Simulation Framework for Supply Chain Modeling: State of the Art and Case Study

Nowadays there is a large availability of discrete event simulation software that can be easily used in different domains: from industry to supply chain, from healthcare to business management, from training to complex systems design. Simulation engines of commercial discrete event simulation software use specific rules and logics for simulation time and events management. Difficulties and limitations come up when commercial discrete event simulation software are used for modeling complex real world-systems (i.e. supply chains, industrial plants). The objective of this paper is twofold: first a state of the art on commercial discrete event simulation software and an overview on discrete event simulation models development by using general purpose programming languages are presented; then a Supply Chain Order Performance Simulator (SCOPS, developed in C++) for investigating the inventory management problem along the supply chain under different supply chain scenarios is proposed to readers.Comment: International Journal of Computer Science Issues online at http://ijcsi.org/articles/A-General-Simulation-Framework-for-Supply-Chain-Modeling-State-of-the-Art-and-Case-Study.ph

Altered motor phenotype and dopamine transmission associated with mutations of the parkinsonian gene LRRK2

The leucine-rich repeat kinase 2 mutation (LRRK2) G2019S in the kinase-domain is the most common genetic cause of late-onset autosomal dominant Parkinson’s Disease (PD), occurring in >85% of patients carrying this LRRK2 mutation. LRRK2-related PD is clinically indistinguishable from the classic idiopathic form, being characterized by classic neuropathological hallmarks such as progressive degeneration of the substantia nigra pars compacta (SNpc) dopaminergic neurons, gliosis and α-synuclein and ubiquitine-positive intraneuronal cytoplasmic inclusions. The main goal of this thesis work was to evaluate the role played by the kinase function of LRRK2 in the expression of motor phenotype and dopamine transmission in mice, since transgenic models reported so far failed to recapitulate the parkinsonian phenotype and its neuropathology. To directly explore the impact of the kinase-enhancing G2019S mutation on motor activity in vivo, a longitudinal phenotyping approach was developed. We enrolled two cohorts of G2019S knock-in (KI) mice and wild-type littermates (WT) and analyzed their motor activity at different ages (3, 6, 10, 15 and 19 months) using a set of complementary behavioral tests, specific for akinesia, bradykinesia and overall gait ability. Our study revealed that G2019S KI mice motor performance remained stable up to the age of 19 months and did not show the typical age-related decline in immobility time and stepping activity of WT. To confirm that enhanced kinase activity accounts for this phenotype, we adopted a combined genetic and pharmacological approach. On one hand we performed a parallel longitudinal study in mice carrying a LRRK2 mutation (D1994S) that impairs kinase activity (kinase-dead, D1994S KD), on the other hand we administered two LRRK2 kinase inhibitors (H-1152 and Nov-LRRK2-11) in G2019S mice. We found that i) KD mice were not phenotypic and ii) LRRK2 inhibitors reversed the hyperkinetic phenotype of G2019S KI mice, while being ineffective in WT or in D1994S KD animals. In vivo LRRK2 targeting of kinase inhibitors was further substantiated by the reduction of LRRK2 phosphorylation at Ser935 in the striatum and/or cortex at efficacious doses of LRRK2 inhibitors. In order to investigate whether the hyperkinetic phenotype of G2019S mice was associated with dysfunction of striatal dopamine neurotransmission, we carried out a series of behavioral, biochemical, and neurochemical experiments. No changes in nigral dopamine cell counts or dopamine striatal density were observed in G2019S mice. However, the overall pattern of responses to a D2/D3 receptor agonist or antagonists and to D1/D5 receptor antagonists suggested an elevated tonic activation of dopamine receptors in G2019S KI mice. Furthermore, blockade of the dopamine transporter (DAT) resulted in an enhancement of motor performance of WT but not G2019S KI mice. Results from in vitro binding assays revealed a reduction in the DAT protein levels which was associated with an increased dopamine reuptake in G2019S KI mice. In vivo microdialysis showed a reduced metabolites/dopamine ratio in in the striatum of G2019S mice, suggesting a reduced dopamine turnover. Overall the data provide genetic and pharmacological evidence that the kinase activity of LRRK2 is highly implicated in the modulation of motor activity along with the striatal dopaminergic system. However, whether and how the observed changes in motor phenotype and dopamine transmission translate into the overt parkinsonian pathology remains a matter for speculation. It is also possible that G2019S KI mice reflect a pre-symptomatic stage of the disease, as observed in other genetic models of PD. Nonetheless, the present thesis work proposes G2019S KI mice as a valuable in vivo model to investigate the effects of LRRK2 inhibitors

Simulation of prompt emission from GRBs with a photospheric component and its detectability by GLAST

The prompt emission from gamma-ray bursts (GRBs) still requires a physical explanation. Studies of time-resolved GRB spectra, observed in the keV-MeV range, show that a hybrid model consisting of two components, a photospheric and a non-thermal component, in many cases fits bright, single-pulsed bursts as well as, and in some instances even better than, the Band function. With an energy coverage from 8 keV up to 300 GeV, GLAST will give us an unprecedented opportunity to further investigate the nature of the prompt emission. In particular, it will give us the possibility to determine whether a photospheric component is the determining feature of the spectrum or not. Here we present a short study of the ability of GLAST to detect such a photospheric component in the sub-MeV range for typical bursts, using simulation tools developed within the GLAST science collaboration.Comment: 12 pages, 5 figures; submitted proceeding for GRB Symposium in Stockholm, Sweden : "Gamma-Ray Bursts: Prospects for GLAST

Split property for free massless finite helicity fields

We prove the split property for any finite helicity free quantum fields. Finite helicity Poincar\'e representations extend to the conformal group and the conformal covariance plays an essential role in the argument. The split property is ensured by the trace class condition: Tr (exp(-s L_0)) is finite for all s>0 where L_0 is the conformal Hamiltonian of the M\"obius covariant restriction of the net on the time axis. We extend the argument for the scalar case presented in [7]. We provide the direct sum decomposition into irreducible representations of the conformal extension of any helicity-h representation to the subgroup of transformations fixing the time axis. Our analysis provides new relations among finite helicity representations and suggests a new construction for representations and free quantum fields with non-zero helicity.Comment: v2: Minor corrections, comments and references added, as to appear in Ann. H. Poin

Institutional public private partnerships for core health services: evidence from Italy.

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.BACKGROUND: Public-private partnerships (PPPs) are potential instruments to enable private collaboration in the health sector. Despite theoretical debate, empirical analyses have thus far tended to focus on the contractual or project dimension, overlooking institutional PPPs, i.e., formal legal entities run by proper corporate-governance mechanisms and jointly owned by public and private parties for the provision of public-health goods. This work aims to fill this gap by carrying out a comparative analysis of the reasons for the adoption of institutional PPPs and the governance and managerial features necessary to establish them as appropriate arrangements for public-health services provisions. METHODS: A qualitative analysis is carried out on experiences of institutional PPPs within the Italian National Health Service (Sistema Sanitario Nazionale, SSN). The research question is addressed through a contextual and comparative embedded case study design, assuming the entire population of PPPs (4) currently in force in one Italian region as the unit of analysis: (i) a rehabilitation hospital, (ii), an orthopaedic-centre, (iii) a primary care and ambulatory services facility, and (iv) a health- and social-care facility. Internal validity is guaranteed by the triangulation of sources in the data collection phase, which included archival and interview data. RESULTS: Four governance and managerial issues were found to be critical in determining the positive performance of the case examined: (i) a strategic market orientation to a specialised service area with sufficient potential demand, (ii) the allocation of public capital assets and the consistent financial involvement of the private partner, (iii) the adoption of private administrative procedures in a regulated setting while guaranteeing the respect of public administration principles, and (iv) clear regulation of the workforce to align the contracts with the organisational culture. CONCLUSIONS: Findings suggests that institutional PPPs enable national health services to reap great benefits when introduced as a complement to the traditional public-service provisions for a defined set of services and goals